An In Vitro Model of Mast Cell Recruitment and Activation by Breast Cancer Cells Supports Anti-Tumoral Responses.

Angélica Aponte-López,Ezequiel M Fuentes-Pananá,Jennifer Enciso,Samira Muñoz-Cruz

doi:10.3390/ijms21155293

Abstract

Breast cancer (BrC) affects millions of women yearly. Mast cells (MCs) are common components of breast tumors with documented agonistic and antagonistic roles in tumor progression. Understanding the participation of MCs in BrC may lead to new therapies to control tumor growth. In this study, we looked into mechanistic models of MC responses triggered by BrC cells (BrCC), assessing both early degranulation and late transcriptional activities. We used aggressive and non-aggressive BrCC to model the progressive staging of the disease over HMC1 and LAD-2 human MC lines. We found that both MC lines were chemoattracted by all BrCC, but their activation was preferentially induced by aggressive lines, finding differences in their active transcriptional programs, both at basal level and after stimulation. Among those genes with altered expression were down-regulated SPP1, PDCD1, IL17A and TGFB1 and up-regulated KITLG and IFNG. A low expression of SPP1 and a high expression of KITLG and IFNG were associated with increased overall survival of BrC patients from public databases. The set of altered genes is more often associated with tumor stromas enriched with anti-tumoral signals, suggesting that MCs may participate in tumor control.

Highlights

Breast cancer (BrC) is an important health problem mainly affecting women of productive age
We found an average of 35.24 pg/mL induced by non-aggressive cells, similar to basal release, and lower than aggressive BrC cells (BrCC); still, this difference was not significant (Supplementary Figure S1C)
We evaluated the kinetics of expression of VEGF and IL-5 finding similar results in IL-5, while expression of VEGF did not change over time (Supplementary Figure S3)

Summary

Introduction

Breast cancer (BrC) is an important health problem mainly affecting women of productive age. In 2018, the World Health Organization estimated more than two million new cases, representing 11.6% of all cancers and the second place in incidence [1]. New approaches for cancer treatment include strengthening the immune system to enforce tumor control. BrC is generally infiltrated by a variety of immune cells that execute both agonistic and antagonistic roles in tumor progression [2,3], with some immune cells playing well-characterized roles. Macrophages favor extracellular matrix degradation and tumor cell invasion, which is associated with poor clinical outcomes. CD8 T cells favor tumor cell cytotoxicity and their presence is associated with good prognosis [2,3,4]. A clear understanding of the molecular mechanisms displayed by immune cells within the tumor stroma will lead to new tools for cancer treatment

Methods

Results

Conclusion